imipramine

(im-ip-ra-meen) {Apo-Imipramine}, {Impril}, Norfranil, {Novopramine}, Tipramine, Tofranil, Tofranil PM CLASSIFICATION(S): Therapeutic: antidepressants Pharmacologic: tricyclic antidepressants Pregnancy Category C
Copyright 2005 by F.A. Davis Company

INDICATIONS

Various forms of depression (with psychotherapy) Enuresis in children. Unlabelled Uses: o Adjunct in the management of chronic pain, incontinence (in adults), vascular headache prophylaxis, and cluster headache.

ACTION

Potentiates the effect of serotonin and norepinephrine Has significant anticholinergic properties. Therapeutic Effects: o Antidepressant action that develops slowly over several weeks.

PHARMACOKINETICS Absorption: Well absorbed from the GI tract. Distribution: Widely distributed. Probably crosses the placenta and enters breast milk. Protein Binding: 8995%. Metabolism and Excretion: Extensively metabolized by the liver, mostly on first pass; some conversion to active compounds. Undergoes enterohepatic recirculation and secretion into gastric juices. Half-life: 816 hr. CONTRAINDICATIONS AND PRECAUTIONS Contraindicated in:

Hypersensitivity Cross-sensitivity with other antidepressants may occur Narrow-angle glaucoma Hypersensitivity to tartrazine or sulfites (in some preparations)

Pregnancy and lactation.

Use Cautiously in: Geriatric patients (more susceptible to adverse reactions) Pre-existing cardiovascular disease Geriatric men with prostatic hyperplasia (more susceptible to urinary retention) Seizures or history of seizure disorder.

ADVERSE REACTIONS AND SIDE EFFECTS*

*CAPITALS indicate life threatening; underlines indicate most frequent.

CNS: drowsiness, fatigue, agitation, confusion, hallucinations, insomnia. EENT: blurred vision, dry eyes. CV: ARRHYTHMIAS, hypotension, ECG changes. GI: constipation, dry mouth, nausea, paralytic ileus. GU: urinary retention. Derm: photosensitivity. Endo: gynecomastia. Hemat: blood dyscrasias. INTERACTIONS DrugDrug: May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent usediscontinue 2 wk prior to imipramine) Concurrent use with SSRI antidepressants may result in increased toxicity and should be avoided ( fluoxetine should be stopped 5 wk before) Concurrent use with clonidine may result in hypertensive crisis and should be avoided Imipramine is metabolized in the liver by the cytochrome P450 2D6 enzyme and its action may be affected by drugs that compete for metabolism by this enzyme including other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics ( propafenone, flecainide); when used concurrently, dosage reduction of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in increased effects of imipramine May prevent the therapeutic response to guanethidine Concurrent use with levodopa may result in delayed/decreased absorption of levodopa or hypertension Blood levels and effects may be decreased by rifamycins

Concurrent use with sparfloxacin increases the risk of adverse cardiovascular reactions Additive CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioid analgesics, and sedative/hypnotics Barbiturates may alter blood levels and effects Adrenergic andanticholinergic side effects may be additive with other agents having these properties Phenothiazines or oral contraceptives increase levels and may cause toxicity Cigarette smoking ( nicotine) may increase metabolism and alter effects.

DrugNatural: Concomitant use of kava, valerian, skullcap, chamomile, or hops can increase CNS depression Increased anticholinergic effects with angels trumpet, jimson weed, and scopolia.

ROUTE AND DOSAGE PO (Adults): 2550 mg 34 times daily (not to exceed 300 mg/day); total daily dose may be given at bedtime. PO (Geriatric Patients): 25 mg at bedtime initially, up to 100 mg/day in divided doses. PO (Children >12 yr): Antidepressant2550 mg/day in divided doses (not to exceed 100 mg/day). PO (Children 612 yr): Antidepressant1030 mg/day in 2 divided doses. PO (Children >6 yr): Enuresis25 mg once daily 1 hr before bedtime; increase if necessary by 25 mg at weekly intervals to 50 mg in children <12 yr, up to 75 mg in children >12 yr. IM (Adults): Up to 100 mg/day in divided doses (not to exceed 300 mg/day).

AVAILABILITY Tablets: 10 mgRx, 25 mgRx , 50 mgRx, 75 mgRx Cost: Tofranil10 mg $34.89/100, 25 mg $56.82/100, 50 mg $100.84/100;generic 10 mg $5.92/100, 25 mg $7.84/100, 50 mg $10.83/100 Capsules: 75 mgRx, 100 mgRx, 125 mgRx, 150 mgRx Injection: 12.5 mg/mlRx. .

TIME/ACTION PROFILE (antidepressant effect) ONSET hours PEAK 26 wk DURATION weeks

PO, IM

NURSING IMPLICATIONS ASSESSMENT General: Monitor blood pressure and pulse rate prior to and during initial therapy. o Monitor baseline and periodic ECGs in elderly patients or patients with heart disease and before increasing dosage with children treated for enuresis. May cause prolonged PR and QT intervals and may flatten T waves. Depression: Assess mental status frequently. Confusion, agitation, and hallucinations may occur during initiation of therapy and may require dosage reduction. Monitor mood changes. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Enuresis: Assess frequency of bedwetting throughout therapy. Pain: Assess location, duration, and severity of pain periodically throughout therapy. Lab Test Considerations: Assess leukocyte and differential blood counts and renal and hepatic functions prior to and periodically during prolonged or highdose therapy. o Serum levels may be monitored in patients who fail to respond to usual therapeutic dose. Therapeutic plasma concentration range for depression is 150300 ng/ml. o May cause alterations in blood glucose levels. Toxicity and Overdose: Symptoms of acute overdose include disturbed concentration, confusion, restlessness, agitation, seizures, drowsiness, mydriasis, arrhythmias, fever, hallucinations, vomiting, and dyspnea. o Treatment of overdose includes gastric lavage, activated charcoal, and a stimulant cathartic. Maintain respiratory and cardiac function (monitor ECG for at least 5 days) and temperature. Medications may include digoxin for CHF, antiarrhythmics, and anticonvulsants.

POTENTIAL NURSING DIAGNOSES

Coping, ineffective (Indications). Urinary elimination, impaired (Indications).

IMPLEMENTATION General: Do not confuse imipramine with desipramine. o Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months. May be given as a single dose at bedtime to minimize sedation during the day. PO: Administer medication with or immediately following a meal to minimize gastric irritation.

IM: May be slightly yellow or red in color. Crystals may develop if solution is cool; place ampule under warm running water for 1 min to dissolve.

PATIENT/FAMILY TEACHING General: Instruct patient to take medication exactly as directed. If a dose is missed, take as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for at least 2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability. o May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known. o Instruct patient to notify health care professional if visual changes occur. Inform patient that periodic glaucoma testing may be needed during long-term therapy. o Caution patient to change positions slowly to minimize orthostatic hypotension. o Advise patient to avoid alcohol or other CNS depressant drugs during therapy and for at least 37 days after therapy has been discontinued. o Instruct patient to notify health care professional if urinary retention occurs or if dry mouth or constipation persists. Sugarless candy or gum may diminish dry mouth and an increase in fluid intake or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk. o Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions. o Inform patient of need to monitor dietary intake, as possible increase in appetite may lead to undesired weight gain. Inform patient that increased amounts of riboflavin in the diet may be required; consult health care professional. o Advise patient to notify health care professional of medication regimen prior to treatment or surgery. o Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to evaluate progress. Children: Inform parents that the side effects most likely to occur include nervousness, insomnia, unusual tiredness, and mild nausea and vomiting. Notify health care professional if these symptoms become pronounced. o Advise parents to keep medication out of reach of children to prevent inadvertent overdose.

EVALUATION

Effectiveness of therapy can be demonstrated by:

Increased sense of well-being o Renewed interest in surroundings o Increased appetite o Improved energy level o Improved sleep in patients treated for depression. Patient may require 26 wk of therapy before full therapeutic effects of medication are noticeable Control of bedwetting in children >6 yr Decrease in chronic neurogenic pain.